This proposal represents a unique collaboration between the disciplines of renal immunomorphology and glomerular pathophysiology, and is designed to provide new information not otherwise attainable. We will define the individual contributions of antibody reactions and their augmenation by biologically active mediator molecules in the genesis and functional consequences of immune forms of glomerular injury. We will amplify our collaborative studies with a new combined in vivo/in vitro approach using the isolated perfused kidney. Individually, glomerular micropuncture and immunomorphologic analysis of experimental models of glomerular injury, even with selected mediator depletion, provide only partial answers to the quantitative contributions of the various interactive mediator pathways. Mediator infusion into the renal artery offers another avenue; however, the mediator still must be viewed in the context of the circulating humoral and cellular milieu. Glomerular hemodynamic analysis of selective mediator effects in vitro in the isolated perfused kidney will be used to supplement the above techniques and couple them with our immunomorphologic and pathophysiologic findings in vivo. Studies will first establish the glomerular hemodynamics of the isolated perfused kidney to provide information about the mechanism of its decreased filtration fraction. Next, glomerular hemogdynamics of nephritic isolated perfused kidneys and kidneys rendered nephritic by ex vivo treatment will be compared with those in vivo. The effect of biological mediator molecules will be correlated using in vivo renal artery infusion and in vitro isolated perfused kidney infusion to quantitate the selective actions. Studies will then progress to assessing glomerular hemodynamics, immunomorphologic correlates, and mediation of immune and chemical injuries in selected glomerular cell populations. Ongoing studies will continue to define additional features of anti-glomerular basement membrane antibody disease, with particular emphasis on factors influencing glomerular-tubular feedback and oxidant injury. Merging of our individual immunomorphologic and glomerular hemodynamic interest has and will provide an increasingly detailed assessment of the correlates of glomerular pathophysiologic change. The combined in vivo and in vitro approach will define the important elements of the immune mechanisms of glomerular injury and the quantitative contribution of mediator systems amenable to therapeutic manipulation.